The work outlined in this grant involes elucidating the biologic importance of a secreted platelet protein, PF-4, and developing ways to study Platelet Factor Four levels in patients with thrombotic disorders. Studies to date have shown that PF-4 is linked to thrombin generation in clotting whole blood and that PF-4 levels are elevated in patients with thrombosis and vascular disease. Recent biochemical studies have shown that PF-4 binds to heparin in a 4:1 complex with a nanomolar KD and that other glycosaminoglycans can compete for heparin binding to PF-4. Studies have also shown that PF-4 binds to glycosaminoglycans on cell surfaces and may also bind to such materials present in the vessel wall. Clinical studies have shown that PF-4 levels are elevated in a variety of thrombotic disorders and, in particular, in patients with coronary artery disease who undergo exercise-induced ischemia. Recent studies have been directed at the effects of drug interventions on preventing this rise in PF-4 in ischemia.